P530: TAGRAXOFUSP IN BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM WITH/WITHOUT CENTRAL NERVOUS SYSTEM INVOLVEMENT AND INTRATHECAL CHEMOTHERAPY AS PRIMARY TREATMENT OR PROPHYLAXIS: AN ITALIAN EXPERIENCE.
Authors: G. Rivoli, G. Beltrami, A. Raiola, A. Dominietto, M. Riggi, E. Angelucci
Journal: HemaSphere (2022)

Background: The precise frequency of central nervous system involvement (CNS+) in patients (pts) with blastic plasmacytoid dendritic cell neoplasm (BPDCN) is currently unknown. Recent small series of clinical experience suggest the incidence to be about 10% at baseline and 30% at first relapse. CNS is a "sanctuary" for any systemic treatment and can lead to disease recurrence even after the achievement of a complete response (CR) at the medullary and skin level. Thus, it is essential to ensure clearance (or prophylaxis) of the disease including the meningeal compartment. Intrathecal (IT) chemotherapy is a valid complementary tool aimed at eradication of the disease, with modest systemic side effects; it is currently indicated as both prophylaxis and primary treatment. Combining IT chemotherapy with systemic treatment has made it possible to obtain long remissions in pts with BPDCN even in the presence of CNS+. Tagraxofusp (TAG), a first-in-class CD123-targeted therapy, was approved by the European Medicines Agency in 2021 for treatment of BPDCN in first-line adult pts. Aims: Data from 5 pts with BPDCN with/without CNS+ treated with TAG were retrospectively collected in our center in Geneva. The aim was to evaluate if CNS treatment/prophylaxis impacts prognosis and efficacy of systemic treatment with TAG. Methods: A diagnosis of BPDCN was confirmed by hematopathology with biomarkers, including CD123, CD4, and CD56, and presence of CNS involvement by the characteristic morphology and "8-color flow cytometry" for CD123. Pts received TAG intravenous infusions at 12 mcg/kg once daily on days 1–5 of a 21-day cycle. TAG was repeated for 1–4 cycles, depending on the level of response and potential bridge to hematopoietic stem cell transplant (HSCT). Hospitalization was mandatory for the first cycle; the following cycles were administered in an outpatient setting if no severe complications occurred during the first cycle. IT chemotherapy (methotrexate 12.5 mg, dexamethasone 4 mg, and cytarabine 50 mg) was administered at each cycle at the same doses until negative cerebrospinal fluid (CSF) was observed in CNS+ pts. After 4 treatment cycles, response was evaluated, including CSF examination. Results: TAG was administered in 5 first-line pts with BPDCN; 3 were CNS+ (1 clinically evident case and 2 with cytofluorometric positivity only). All pts received IT chemotherapy, both as a primary-intention treatment in the 3 CNS+ pts, and as prophylaxis in the 2 CNS-negative pts. Table 1 reports the main pt characteristics. Pts 2, 3, and 5 with CNS+ achieved clearance of the disease and none reported CNS relapse. In pts receiving CNS prophylaxis, pt 1 received TAG plus HSCT and is in CR after 29 months; pt 4 received high-dose chemotherapy, achieved a good partial remission after TAG, and remains alive after 4 months with HSCT shortly planned. No pts developed CNS adverse events following IT chemotherapy. Image:Summary/Conclusion: These preliminary results confirm the feasibility of IT chemotherapy with systemic TAG. Baseline disease and CNS involvement did not appear to predispose pts to different efficacy results or treatment-related adverse events. IT chemotherapy effectively cleared and controlled CNS involvement. IT prophylaxis should be considered in pts with BPDCN who receive CD123-targeted therapies.